1. Field of the Invention
This invention relates to compositions of matter classified in the art of chemistry as esters of 3-(hydroxy or hydroxymethyl)-4-hydroxy-alpha-(aminomethyl)benzyl alcohols, to a process and intermediates for the preparation of the same, and to a method for producing sympathomimetic effects, for instance, bronchodilation, of long duration in warm-blooded animals by administering said esters.
2. Description of the Prior Art
H. Bretschneider, Monatshefte fur Chemie 76, 368-380 (1947) discloses in most pertinent part 3',4'-dibutyryloxy-2-(methylamino)acetophenone and 3',4'-dipropionyloxy-2-(isopropylamino)acetophenone.
H. Bretschneider, Monatschefte fur Chemie 77, 385-397 (1947) discloses in most pertinent part 3,4-bis-(propionyloxy)-alpha-(isopropylaminomethyl)benzyl alcohol, and 3,4-bis(propionyloxy)-alpha-(isopropylaminomethyl)benzyl propionate.
H. Bretschneider, Monatschefte fur Chemie 78, 71-81 (1948) discloses in most pertinent part 3',4'-dibenzoyloxy-2-(methylamino)acetophenone.
Austrian Pat. No. 230,352, published Dec. 10, 1963 discloses in most pertinent part a group of substituted alpha-(alkylaminomethyl)benzyl alcohols having the formula: ##STR1## wherein inter alia:
X is a hydroxyl group or an acyloxy group derived from an aliphatic carboxylic acid containing from 2 to 6 carbon atoms;
Y is an acyloxy group derived from an aliphatic carboxylic acid containing from 2 to 6 carbon atoms;
Z is hydrogen; and
R is alkyl. The most pertinent species disclosed is 3,4-diacetoxyphenyl-2-isopropylamino-ethanol.
G. Zolss, Sci. Pharm. 32, 76-92 (1964) discloses a group of 3,4 and 3,5-diacyloxy-alpha-(aminomethyl)benzyl alcohols including the following pertinent species: ##STR2##
__________________________________________________________________________ R.sub.1 R.sub.2 R.sub.3 R.sub.4 __________________________________________________________________________ CH.sub.3 CO.sub.2 CH.sub.3 CO.sub.2 H CH(CH.sub.3).sub.2 (CH.sub.3).sub.3 CCO.sub.2 (CH.sub.3).sub.3 CCO.sub.2 H H (CH.sub.3).sub.2 CHCH.sub.2 CO.sub.2 H (CH.sub.3).sub.2 CHCH.sub.2 CO.sub.2 CH(CH.sub.3).sub.2 CH.sub.3 (CH.sub.2).sub.7 CO.sub.2 H CH.sub.3 (CH.sub.2).sub.7 CO.sub.2 H CH.sub.3 (CH.sub.2).sub.10 CO.sub.2 H CH.sub.3 (CH.sub.2).sub.10 CO.sub.2 H __________________________________________________________________________
O. Thoma et al. U.S. Pat. No. 3,341,594, issued Sept. 12, 1967 discloses in pertinent part a group of 3,5-disubstituted-alpha-(alkylaminomethyl)benzyl alcohols and 3',5'-disubstituted-2-aminoacetophenones having the respective formulas: ##STR3## wherein inter alia
R' is acyl; and
R" is hydrogen. The patent discloses no examples of compounds having either of the above formulas wherein R' is acyl.
A. Mentrup et al. U.S. Pat. Ser. No. 3,657,244, issued Apr. 18, 1972, application filed Oct. 16, 1967, discloses in most pertinent part a group of 2,3,4-trisubstituted-alpha-(alkylaminomethyl)benzyl alcohols and 2',3',4'-trisubstituted-2-(alkylamino)acetophenones having the respective formulas ##STR4## wherein inter alia:
R.sub.1 is acyl;
R.sub.2 is straight or branched alkyl of 1 to 5 carbon atoms;
R.sub.3 is hydrogen or lower alkyl; and
R.sub.4 is straight or branched alkyl of 1 to 8 carbon atoms or cycloalkyl of 3 to 7 carbon atoms. The most pertinent species disclosed is 1-(2-methyl-2,3,4-diacetoxyphenyl)-2-isopropylamino-ethanol.
Draco, Lunds Farmacevtiska AB Netherlands patent publication 6,714,191, published Apr. 22, 1968 discloses in most pertinent part 3,5-disubstituted-alpha-(alkylaminomethyl)benzyl alcohols and 3',5'-disubstituted-2-(alkylamino)acetophenones having the respective formulas ##STR5## wherein inter alia:
R is tert-butyl or cycloalkyl having from 3 to 6 carbon atoms;
R.sub.3 is an acyl group of not more than 5 carbon atoms; and
R.sub.4 is hydrogen. Specifically disclosed are 3,5-diacetoxy-alpha-(tert-butylaminomethyl)benzyl alcohol and 3',5'-diacetoxy-2-(benzyl-tert-butylamino)acetophenone.
W. Saari et al. U.S. Pat. Ser. No. 3,714,229, issued Jan. 30, 1973, application filed July 10, 1969, discloses, in most pertinent part, substituted-alpha-(1-aminoethyl)benzyl alcohols having the formula ##STR6## wherein inter alia:
R.sup.1 is hydrogen or R.sup.2 CO
R.sup.2 is hydrogen, alkyl, cycloalkyl, alkenyl, phenyl, substituted phenyl or heteroaryl;
R.sup.3 is hydrogen or lower alkyl; and
X is R.sup.2 CO.sub.2. Also disclosed as intermediates are the compounds having the formula ##STR7## wherein R.sup.1 and X have the above-given meaning and R.sup.3 is methyl or ethyl. The patent contains no examples of compounds having either of the above formulas wherein X is a carboxylic ester group.
J. W. Daly et al., J. Med. Chem. 9, 273 (1966) disclose 3,4-dibenzoxy-N-methylphenethylamine hydrochloride.